It has been well established that histones are subject to structural modifications after their synthesis. These changes include acetylation, and phosphorylation which tend to decrease their basic charge, methylation tends to increase the basic charge and hydrophobicity of thus modified residues. Recent studies by the applicant have indicated that histone methyl groupw turn over at the same rate as the histone peptide. This, and the fact that histone methylation occurred primarily at the end of the S-phase of the cell cycle would suggest that methylation of histones would represent some kind of locking mechanism, increasing the affinity between regions of DNA and histone molecules, which have already interacted durinn S-phase. Since uncovering of and subsequent transcription of the wrong information would interfere with normal function in the cell, a study is proposed on the effect of carcinogenesis and carcinogenic agents on histone methylation, to see if any interference with the normal methylation process may be present. The proposed study will focus on the following problems: 1. The effect of carcinogenic and intercalating agents on methylation of histones in vitro. 2. The effect of carcinogenic and intercalating agents on histone methylation in vivo. 3. Alkylation of histones by carcinogens.